The objective of this project is to gain an understanding of the transformation process between different stages of animal parasitic hemoflagellates. We have found that mammalian and insect hosts of hemoflagellate parasites produce inhibitor and/or inducer factors which may regulate the transformation of these organisms from one stage to the next in the life cycle. The specific objectives will involve: 1. A study of the mammalian factor(s) in infected host sera that inhibits transformation of Trypanosoma cruzi (the agent for Chagas' Disease) from the blood stream trypomastigote to the insect midgut amastigote and to study the insect cell factor(s) responsible for inducing transition from insect amastigote stage to metacyclic trypomastigote stage. 2. An in vitro analysis of respiratory metabolism at 37 degrees C of Leishmania donovani (the agent for visceral leishmaniasis (kala azar)) vertebrate stage amastigotes inhibited from transforming by infected hamster spleen blocking factor(s). 3. A study of changes in polyamine (putrescine, spermidine and spermine concentration and ornithine decarboxylase (the first enzyme involved in the polyamine synthetic pathway) activity in L. donovani before, during and after transformation from the vertebrate amastigote to the insect (and/or culture) promastigote stage and to correlate these with changes in parasite membrane activity (e.g., sensitivity to ionophores). The information obtained from these studies will be of significance in understanding host regulation of hemoflagellate development and of value for devising new rational modes of control for Chagas' Disease and Kala azar.